Journal of Gastroenterology

, Volume 41, Issue 4, pp 369–377

Farnesoid X receptor, hepatocyte nuclear factors 1α and 3β are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene

Authors

  • Hideo Ohtsuka
    • Division of Gastroenterological Surgery, Department of SurgeryTohoku University Graduate School of Medical Science
  • Takaaki Abe
    • Divisions of Nephrology, Endocrinology, and Vascular Medicine, Department of MedicineTohoku University Graduate School of Medical Science
    • PRESTOJapan Science and Technology Corporation (JST)
  • Tohru Onogawa
    • Division of Gastroenterological Surgery, Department of SurgeryTohoku University Graduate School of Medical Science
  • Noriko Kondo
    • Division of Gastroenterological Surgery, Department of SurgeryTohoku University Graduate School of Medical Science
  • Takeaki Sato
    • Division of Gastroenterological Surgery, Department of SurgeryTohoku University Graduate School of Medical Science
  • Hiroshi Oshio
    • Division of Gastroenterological Surgery, Department of SurgeryTohoku University Graduate School of Medical Science
  • Hiroya Mizutamari
    • Division of Gastroenterology, Department of MedicineTohoku University Graduate School of Medical Science
  • Tsuyoshi Mikkaichi
    • PRESTOJapan Science and Technology Corporation (JST)
  • Masaya Oikawa
    • Division of Gastroenterological Surgery, Department of SurgeryTohoku University Graduate School of Medical Science
  • Toshiki Rikiyama
    • Division of Gastroenterological Surgery, Department of SurgeryTohoku University Graduate School of Medical Science
  • Yu Katayose
    • Division of Gastroenterological Surgery, Department of SurgeryTohoku University Graduate School of Medical Science
  • Michiaki Unno
    • Division of Gastroenterological Surgery, Department of SurgeryTohoku University Graduate School of Medical Science
Article

DOI: 10.1007/s00535-006-1784-3

Cite this article as:
Ohtsuka, H., Abe, T., Onogawa, T. et al. J Gastroenterol (2006) 41: 369. doi:10.1007/s00535-006-1784-3

Abstract

Background

We isolated the human liver-specific organic anion transporter gene, LST-2 (OATP8/SLCO1B3), which is exclusively expressed in the basolateral membrane of the hepatocytes. In this study, we analyzed the transcriptional regulation of the LST-2 gene in hepatocyte-derived cells and the effect of bile acid.

Methods

Transcriptional activity of the LST-2 gene was measured using a human LST-2 promoter–luciferase reporter plasmid under various concentrations of bile acids. Electrophoresis mobility shift assays of farnesoid X receptor (FXR), hepatocyte nuclear factor (HNF) 1α, and HNF3β were performed.

Results

Luciferase analysis showed that the 5′-flanking region from −180 to −20 bp is responsible for LST-2 transcriptional activity. By site-directed mutation analysis, it was revealed that the consensus binding sites for FXR, HNF1α, and HNF3β play important roles in the transcriptional activity of the LST-2 gene. By electrophoresis mobility shift assay, we observed specific protein–DNA complexes of FXR, HNF1α, and HNF-3β. Luciferase activity was increased fivefold when chenodeoxycholate or deoxycholate were added. Northern blot analyses revealed that the expression of LST-2 was increased by addition of chenodeoxycholate or deoxycholate in a dose-dependent manner.

Conclusions

This study demonstrated that the transcription of the LST-2 gene is regulated by three transcription factors, FXR, HNF1α, and HNF3β. HNF1α and HNF3β might contribute to its liver-specific expression, and FXR might play a role in its transcriptional activation by bile acids.

Key words

organic anion transportertranscription factorbile acidHep3BTHLE-3

Copyright information

© Springer-Verlag Tokyo 2006